Major depressive disorder is a significant public health problem, disproportionately affecting women. Approximately 70% of patients do not respond or only partially respond to standard SSRI treatment despite adequate dosing. In our open-label pilot data, two-thirds of women with major depressive disorder who were resistant or partially resistant to antidepressants achieved a response to very low-dose, physiologic transdermal testosterone administration; one-third of women treated achieved remission after 8 weeks of therapy, with no hyperandrogenic side effects. We propose a collaborative, randomized, placebo-controlled trial to determine whether larger, multi-center trials are indicated to investigate whether low-dose testosterone is an efficacious and well-tolerated augmentation strategy in women with major depressive disorder and SSRI partial/nonresponse. We propose a collaborative, multidisciplinary study from two academic medical centers in order to increase sample size, accelerate recruitment and increase sample diversity.